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INSTRUCTION

Examine this patient's chest.Examine this patient's chest from the back.Examine this patient's chest from the front.

SALIENT FEATURES

History

• Fever.

• Pleuritic pain (made worse on coughing or deep breathing).

• Cough (pneumonia, TB).

• Haemoptysis (associated parenchymal involvement in bronchogenic carcinoma or TB).

• Shortness of breath (large effusions, cardiac failure).

• Exposure to asbestos (mesothelioma).

• Nephrotic syndrome.

Examination

• Decreased movement on the affected side.

• Tracheal deviation to the opposite side.* Stony dull note on the affected side.

• Decreased vocal resonance and diminished breath sounds on the affected side.

Proceed as follows:

• Comment on aspiration marks.

• Percuss for the upper level of effusion in the axilla.

• Listen for bronchial breath sounds.

• Listen for aegophony at the upper level of the effusion.

• It is important to elicit any evidence of an underlying cause, such as clubbing, tar staining, lymph nodes, radiation burns andmastectomy, raised JVP, rheumatoid hands or butterfly rash.

• Remember. 500 mi of pleural fluid should be present for clinical detection and there are 5 major types of pleural effusion: exudate,transudate, empyema, haemor-rhagic pleural effusion or haemothorax, and chylous effusion.

DIAGNOSIS

This patient has a pleural effusion (lesion), probably due to bronchogenic carci-noma, and is short of breath at rest (functionalstatus).Read review: Postgrad Med d 1993; 69:12 18; Thorax 1979: 304: 106.

QUESTIONS

How would you investigate this patient?

Chest radiography (CXR)Standard posteroanterior and lateral chest radiographs detect pleural fluid in excess of 175 ml. Obliteration of costophrenic angle tohemithorax suggests fluid. Sub-pulmonic effusion can simulate an elevated diaphragm.Pleural tap· Pleural fluid for determination of the levels of protein, albumin, LDH, glucose, cholesterol and cytology. A simultaneous bloodsample should be obtained for estimation of glucose, protein, albumin and LDH.· When empyema is suspected or seen, pleural fluid pH should be obtained.· When tuberculosis is suspected, pleural fluid adenosine deaminase or lysozyme levels should be determined andZiehl-Neelsen staining and pleural fluid myco-bacterial cultures should be done.· Pleural fluid amylase levels should be estimated when malignancy, pancreatitis or oesophageal rupture is suspected.· In autoimmune disorders, pleural fluid rheumatoid factor or antinuclear anti-bodies should be tested.P!eural biopsyThe biopsy specimen is sent for histopathological examination and mycobacterial culture.

What are the causes of dullness at a lung base?

• Pleural effusion.

• Pleural thickening.

• Consolidation and collapse of the lung.

• Raised hemidiaphragm.

How would you differentiate between the above?

• Pleural effusion: stony dull note; trachea may be deviated to the opposite side in large effusions.

• Pleural thickening: trachea not deviated; breath sounds will be heard.· Consolidation: vocal resonance increased; bronchial breath sounds and associated crackles.

• Collapse: trachea deviated to the affected side; absent breath sounds.

How would you differentiate between an exudate and a transudate?

The protein content of an exudate is more than 3 g/l. However, if this criterion alone is applied, about 10% of the exudates and15% of the transudates will be wrongly classified. A more accurate diagnosis is made when Light's criteria (Ann Intern Med1972; 77: 507-13) for an exudate are applied: (1) the ratio of the pleural fluid to serum protein is greater than 0.5; (2) the ratio ofpleural fluid to serum lactic dehydrogenase (LDH) is greater than 0.6; (3) pleural fluid LDH is greater than two thirds the uppernormal limit for blood LDH levels. Roth et al (1990) found that, althomzh Light's criteria had a sensitivity of 100%, they had alow specificity of 72% (Chest 1990; 98: 546-9). This was due to the fact that many patients with effusion due to chronic cardiacfailure have protein values inthe exudate range, particularly when on chronic diuretic therapy. They found that the serum-effusion albumin gradient (i.e. serumalbumin minus pleural fluid albumin) was 95% sensitive but a more specific (100%) marker of exudative effusion. A gradient of lessthan 1.2 g/dl indicates an exudative effusion whereas a gradient greater than 1.2 g/dl indicates a transudative effusion.· The pleural fluid cholesterol level is below 60 mg/dl in transudates. All malignant effusions have a pleural cholesterol levelgreater than this value, and therefore this test is useful to separate these two categories of effusion (Chest 1987; 92: 296-302;Chest1991; 99: 1097-102).

Mention a few causes for an exudate and a transudate.

Causes for an exudate:

· Bronchogenic carcinoma (presence of effusion is an ominous sign).· Secondaries in the pleura (lung, breast, ovary and pancreas).· Pneumonia.· Pulmonary infarction.· Tuberculosis.· Rheumatoid arthritis.· SLE.· Lymphoma (in young individuals).· Mesothelioma.

Causes of a transudate:

• Nephrotic syndrome.

• Cardiac failure.

• Liver cell failure.

• Hypothyroidism.

ADVANCED-LEVEL QUESTIONS

Mention a few conditions in which the pleural fluid pH and glucose levels are Iow with a raised LDH concentration.

Empyema, malignancy, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus and oesophageal rupture.

What is the value of measuring pleural fluid pH and glucoseconcentrations in cases of malignant effusions?

This is of value in determining the prognosis (Ann Intern Med 1988; 108: 345-9).Patients with a low pleural fluid pH (<7.3) or low glucose concentration (<60 mg/dl) have a shorter life expectancy than those withhigher values: 2.1 months versus 9.8 months. The low pH group tends to have more extensive pleural involvement as determined bythoracoscopy and a higher failure rate for chemical pleurodesis.

What further investigation would you perform to determine the underlying cause of the pleural effusion?

• Pleural biopsy.

• CT chest scan.

• Magnetic resonance imaging of the chest: although this technique has limited value owing to motion artefacts caused bycardiac and respiratory movements,radiologists were able to differentiate transudates, simple exudates and complex exudates.

What is the role of pleural fluid cytology in the diagnosis of pleural effusion ?

• Pleural fluid usually contains about 1500 cells per gl (predominantly mono-nuclear cells). Counts above 50 000 are seen inparapneumonic effusions, whereas transudates usually have counts of less than 1000 cells per Itl.

• Pleural fluid eosinophilia, i.e. greater than 10%, suggests a benign disease, including pneumothorax, asbestos-relatedeffusions and post haemothorax, although malignancy cannot be excluded.

• Pleural fluid lymphocytosis is seen in about one third of transudates, in malignancy, tuberculosis, lymphoma, collagen vasculardiseases and sarcoidosis.

• Computerized interactive morphometry (analyses the size and nuclei of cells in a stained centrifuged specimen)differentiates between malignant cells and reactive lymphocytosis. This method is particularly useful when differentiatingbetween benign reactive mesothelial cells and malignancy.

What characteristics of the pleural fluid in a parapneumonic effusion indicate a need for closed-tube drainage?

A pleural fluid glucose concentration of less than 40 mg/dl or a pH less than 7.0 indicates the need/¥r closed-tube drainage.

What does a pleural fluid total neutral fat level greater than400 mg/dl suggest?

It suggests chylothorax and is seen most often in patients with lymphomas, solid tumours, nephrotic syndrome and cirrhosis, andoccasionally in rheumatoid arthritis.

What is the significance of pleural fluid amylase levels?

A pleural fluid amylase level greater than the serum amylase concentration is seen in patients with pancreatitis, carcinoma, bacterialpneumonia and oesophageal rupture. In malignant effusions, when cytology cannot differentiate adenocarcinoma frommesothelioma, a raised amylase level suggests the presence of the former. Amylase-rich pleural effusions occur frequently, andpleural fluid isoamylase determination can be useful; the finding of a pleural effusion rich in salivary isoamylase should prompt anevaluation for carcinoma (particularly a lung primary), but may also be seen in other pleural inflammatory conditions (Chest 1992;102: 1455-9).

What are the causes of an exudate with negative cytology findings and pleural fluid lymphocytosis?

Possible causes include tuberculosis, collagen vascular diseases and tumours, including lymphoma.

In such patients, what other tests could you perform on the pleural fluid to determine the underlying cause?

• Pleural fluid adenosine deaminase concentration (an enzyme involved in purine metabolism and found in T lymphocytes) ismarkedly raised in tuberculous and rheumatoid effusions compared with malignant effnsion

• Increased pleural fluid lysozyme concentration (muramidase) is used to differ-entiate tuberculosis, rheumatoid arthritis andempyema from malignant effusions.

• Combined use of the latter two tests yields a sensitivity and specificity of 100% for tuberculous et'tusions if empyema ~sexcluded.

• Gamma-interferon and soluble interleukin 2 receptor levels are also raised in tuberculous effusions compared with malignanteffusions.

• Estimation of pleural fluid rheumatoid factor and antinuclear antibodies is useful in confirming the diagnosis of rheumatoid andlupus erythematosus respectively.

In which conditions is the pleural fluid bloody?

Haemorrhagic fluid is seen in malignancy, pulmonary embolus, tuberculosis and trauma to the chest.

What are the earliest radiological signs of pleural fluid?

The earliest radiological signs are blunting of the costophrenic angle on the anterior-posterior view or loss of clear definition of thediaphragm posteriorly on the lateral view.

How would you confirm your suspicions when in doubt of a small effusion ?

Either by a lateral decubitus view (which shows a layering of the fluid along the dependent chest wall unless the fluid is loculated) orby ultrasonography.

What are the other uses of ultrasonography in the diagnosis of pleural effusion ?

Ultrasonography is also useful for loculated effusions, for guided thoracocentesis, closed pleural biopsy or insertion of a chest drain,and to differentiate pleural fluid from pleural thickening.

What is a pseudotumour?

It is the accumulation of fluid between the major or minor fissure or along the lateral chest wall, and can be mistaken for a tumour onthe radiograph. Such loculated effusions can be confirmed with ultrasonography.

What do you know about pleural disease in rheumatoid arthritis?

About 70% of patients with rheumatoid arthritis have pleural inflammation at autopsy and about 5% have radiological evidence ofpleural inflammation at some time. Pleural involvement is associated with male sex, rheumatoid factor in serum, the presence ofnodules and other systemic manifestations. The effusion is thought to develop as an inflammatory response to the presence ofmultiple subpleural nodules. For reasons that are entirely unclear, the left side is the more common site of unilateral rheumatoidpleural effusions. The pleural fluid glucose level is characteristically low and is said to be due to an 'entrance block' in which glucoseis unable to enter the pleural space, unlike in empyema and malignant effusions where the low pleural fluid glucose concentration isattributed to the increased use of glucose by cells. Cytological appearances of slender and elongated macrophages, round giantmultinucleated macrophages, presence of very few mesothelial cells and necrotic background material are thought to bepathognomonic of rheumatoid pleuritis.

What are the complications of thoracocentesis?

Pneumothorax, haemothorax, intravascular collapse and unilateral pulmonary oedema (the latter after withdrawal of large quantitiesof fluid).

What do you know about Meigs' syndrome?

Meigs' syndrome comprises pleural effusion (usually right-sided and a transudate) associated with ovarian tumours (usually benignovarian fibroma).

Mention some causes of drug-induced pleural effusion.

Practolol, procarbazine, methysergide, bromocriptine, methotrexate andnitrofurantoin.

The patient used to be a shipbuilder: what diagnosis would you consider?

It is most likely that this patient has malignant mesothelioma. If' the diagnosis is confirmed, I would advise him to apply for industrialinjuries benefit.

What are the mechanisms for abnormal accumulation of pleural fluid?

There are three main mechanisms:· An abnormality of the pleura itself, such as a neoplasm or inflammatory process, usually associated with increasedpermeability.· Disruption of the integrity of a fluid-containing structure within the pleural cavity, such as the thoracic duct, oesophagus, majorblood vessels or tracheobronchial tree, with leakage of the contents into the pleural space.· Abnormal hydrostatic or osmotic forces operating on an otherwise normal pleural surface and producing a transudate.